Reconstruction of the hematopoietic system using bone marrow, thymus, and spleen organoids: Construction strategies and research advances

Hematopoietic development and systemic homeostasis depend critically on specific three-dimensional (3D) microenvironments within the bone marrow, thymus, and spleen. Traditional two-dimensional (2D) cultures and animal models frequently fail to recapitulate human physiology due to spatial limitations and interspecies genetic divergence. While 3D organoids offer a compelling alternative, achieving anatomical fidelity and sustaining long-term functionality remain significant bioengineering hurdles. Navigating these challenges, this review synthesizes emerging strategies for constructing high-fidelity hematopoietic organoids. We detail engineered bone marrow constructs tailored to model osteo-vascular niches and sustain hematopoietic stemness, seamlessly paired with thymic platforms reconstructing epithelial microenvironments for directed lymphopoiesis. Shifting to systemic dynamics, we evaluate nascent spleen organoids simulating hemodynamics, erythroid clearance, and extramedullary hematopoiesis. By capturing dynamic circulation, these biomimetic tools establish a transformative paradigm for elucidating hematological mechanisms, accelerating drug screening, and advancing personalized medicine.